This application is prepared in response to RFA-ES-15-009: Children's Health Exposure Analysis Resource (CHEAR): National Exposure Assessment Laboratory Network (U2C), and, if funded, will be one of several CHEAR Hubs designed to provide exposure assessment marker measurements and biological response indicator measurements to epidemiological and clinical investigators. The ultimate goal of the RTI International CHEAR Hub is to develop a self-sustaining Hub that will maintain and develop state-of-the- art standardized methods and promote research, training, and education in assessment of exposure and response. The RTI CHEAR Hub will work within the CHEAR Network and with other CHEAR Hubs, the CHEAR Data Repository and Analysis Science Center (DRASC), and the CHEAR Coordinating Center (CC) to develop new methods; to refine existing methods to lower concentrations and new matrices; to provide guidance on study design, sample collection, and storage; and to provide services for targeted, untargeted, and biological response measurements. This proposal provides a description of the capabilities, experiences, and approaches that will be used in the Targeted Analysis Resource Core (TARC, Leader Keith Levine), the Untargeted Analysis Resource Core (UARC, Leader Susan Sumner), and the Biological Response Indicator Core (BRIC, Co-Leaders Robert Clark and Leslie Recio). Refinement of existing methods and the development of new analytical and biological approaches to assess the impact of environmental exposure will be conducted by the Development Core (DC, Leader Timothy Fennell). The Administrative Core will provide oversight for interactions with the CHEAR Program and will ensure that timelines, budgets, and staffing are appropriate for the studies to be performed. RTI has decades of experience in exposure assessment and has a history of conducting research in children's health. The RTI CHEAR Hub, directed by Dr. Timothy Fennell, is strengthened by the untargeted analysis capabilities of the NIH Eastern Regional Comprehensive Metabolomics Resource Core (RTI RCMRC, directed by Dr. Susan Sumner) and our partnership with Dr. Oliver Fiehn who directs the West Coast RCMRC at University of California at Davis and is experienced in conducting metabolomics for large cohort studies. Our partners at Integrated Laboratory Systems (Directed by Dr. Leslie Recio) bring additional in-depth strengths for the measurement of biological response indicators. The overall goal of the CHEAR Program will be to provide resources and services for use in epidemiological and clinical investigations to enable analysis of a wide range of biospecimens using state-of-the-art technologies to understand the influence of the environment on disease.